HOUSTONAmifostine (Ethyol) can reduce the risk of acute pneumonitis
and severe esophagitis associated with concurrent radiation and chemotherapy
administered to patients with advanced non-small-cell lung cancer (NSCLC).
Results of a phase III study were reported by Ritsuko Komaki, MD, professor
of radiation oncology at the University of Texas M.D. Anderson Cancer Center
in Houston.

"The purpose of this trial was to compare esophageal toxicity of
grade 3 to 4, including severe dysphagia and odynophagia, in patients who
received chemoradiotherapy with or without amifostine. The trial also
compared hematologic and pulmonary toxicity. Secondary endpoints were
survival, local control and distant metastasis," Dr. Komaki said.
Toxicities were scored using Radiation Therapy Oncology Group (RTOG)
criteria. The study was designed with the power to detect a 50% reduction in
the rate of severe acute esophagitis.

Amifostine was chosen for this study because it has protective abilities
against nephrotoxicity, hematologic toxicity, neurologic toxicity, and
radiation-induced injury, Dr. Komaki explained.

Eligibility criteria included medically inoperable stage II and stage
IIIA or IIIB NSCLC, no major weight loss, and no pleural effusion, prior
chemotherapy, or prior radiation therapy. "We had only two patients
with medically inoperable stage II disease. The majority of the patients
were surgically inoperable stage IIIB," Dr. Komaki said.

Randomized to Two Arms

Twenty-seven patients were randomized to arm I (chemoradiation with
amifostine) and 26 were randomized to arm II (chemoradiation without
amifostine). Patients in arm I received amifostine, 500 mg IV over 5
minutes, 15 minutes before cisplatin (Platinol) infusion on days 1, 8, 29,
and 36, and 500 mg IV over 5 minutes, 30-60 minutes before the first daily
fraction of radiation on days 2, 9, 15, 16, 22, 23, 30, and 37.

"The regimen was slightly different from that in RTOG 98-01. We used
oral etoposide and cisplatin and radiation therapy in 1.2 Gy twice-daily
fractionations, with a 6-hour interfractional interval, and the total tumor
dose of 69.6 Gy. There was no induction chemotherapy," Dr. Komaki said.
"We gave the amifostine at 7 o’clock in the morning."